The apelinergic system: Sexual dimorphism and tissue-specific modulations by obesity and insulin resistance in female mice |
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| Institution: | 1. Université Lille Nord de France, Unité Environnement Périnatal et Croissance, EA 4489, Faculté de Médecine, Pôle Recherche, IFR 114, 59045 Lille, France;2. Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 3, INSERM U1048, 31432 Toulouse, France;1. School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, China;2. Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, Jilin 130021, China;3. College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, China;1. Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon;2. Institute of Community and Public Health, Birzeit University, Birzeit, occupied Palestinian territory;3. Brown University, Providence, RI, USA;4. United Nations Economic and Social Commission for Western Asia, Beirut, Lebanon;5. Social Research Center, American University in Cairo, New Cairo, Egypt;6. Faculty of Arts and Sciences, Boğaziçi University, Istanbul, Turkey;1. Social Research Center, American University in Cairo, New Cairo 11835, Egypt;1. Department of Health Promotion and Community Health, WHO Collaborating Center for Health Promotion and Behavioral Sciences, Faculty of Health Sciences, American University of Beirut, Beirut 1107 2020, Lebanon;2. Department of Epidemiology, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA;3. Syrian Center for Tobacco Studies, Aleppo, Syria |
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| Abstract: | It has been proposed that the apelinergic system (apelin and its receptor APJ) may be a promising therapeutic target in obesity-associated insulin resistance syndrome. However, due to the extended tissue-distribution of this system, the therapeutic use of specific ligands for APJ may target numerous tissues resulting putatively to collateral deleterious effects. To unravel specific tissular dysfunctions of this system under obesity and insulin-resistance conditions, we measured the apelinemia and gene-expression level of both apelin (APL) and APJ in 12-selected tissues of insulin-resistant obese female mice fed with a high fat (HF) diet. In a preliminary study, we compared between adult male and female mice, the circadian plasma apelin variation and the effect of fasting on apelinemia. No significant differences were found for these parameters suggesting that the apelinemia is not affected by the sex. Moreover, plasma apelin level was not modulated during the four days of the estrous cycle in females. In obese and insulin-resistant HF female mice, plasma apelin concentration after fasting was not modified but, the gene-expression level of the APL/APJ system was augmented in the white adipose tissue (WAT) and reduced in the brown adipose tissue (BAT), the liver and in kidneys. BAT apelin content was reduced in HF female mice. Our data suggest that the apelinergic system may be implicated into specific dysfunctions of these tissues under obesity and diabetes and that, pharmacologic modulations of this system may be of interest particularly in the treatment of adipose, liver and renal dysfunctions that occur during these pathologies. |
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| Keywords: | Apelin/APJ Sexual dimorphism Mouse Obesity Diabetes |
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